An evaluation of the role of Src in renal cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 358-358
Author(s):  
T. Qayyum ◽  
P. A. McArdle ◽  
M. Seywright ◽  
D. C. Mcmillan ◽  
M. Aitchison ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Renal Cancer ◽  
Family Members ◽  
High Expression ◽  
Membrane Expression ◽  
Cancer Specific Survival ◽  
Expression Levels ◽  
Nuclear Expression ◽  
Specific Inhibitors

358 Background: The aim of the current study was to assess the expression levels of c-Src, phosphorylated Src, dephosphorylated c-Src at 530 and the downstream marker Fak 861 in renal cancer. Methods: In all, 60 patients undergoing potentially curative nephrectomy for localised renal cancer were included. Imunohistochemical staining was utilised to assess expression of c-Src, dephosphorlated c-Src at 530, phosphorylated Src at the Y416 site, and Fak 861. Expression was assessed using the weighted histoscore method. Results: High membrane c-Src was associated with increased cancer specific survival (p=0.032). In addition, increased cancer-specific survival was associated with high levels of cytoplasm and membrane expression of c-Src (p=0.039). When assessed individually, membrane, cytoplasm and nuclear expression of phosphorylated Src was not significantly associated with cancer specific survival. However when membrane and cytoplasm expression was combined, high expression was associated with decreased cancer specific survival (p=0.001). Low cytoplasm Fak expression was associated with increased cancer specific survival (p=0.029). When expression of Fak was combined with phosphorylated Src, high expression was associated with decreased cancer specific survival (p=0.003). When taking together high membrane c-Src and phosphorylated Src expression, this was associated with increased cancer specific survival (p=0.029). On multivariate analysis, combined expression of membrane c-Src and phosphorylated Src (HR 0.49, 95% CI 0.24-0.99, p=0.047) and combined Fak and phosphorylated Src expression (HR 1.88, 95% CI 1.06-3.34, p=0.030) were significant independent predictors of cancer specific survival. Conclusions: The results suggest that activated c-Src is associated with improved survival and activated Src family members are associated with decreased survival. This would suggest that another member of the Src family maybe associated with decreased survival. Further work is required to identify which of the Src family members are expressed in renal cancer and would therefore allow specific inhibitors for these Src family members to be developed. No significant financial relationships to disclose.

scholarly journals Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 61366-61377 ◽  
Author(s):  
Zhao Li ◽  
Wenzhuo Zhu ◽  
Liwen Xiong ◽  
Xiaobo Yu ◽  
Xi Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Small Cell ◽  
High Expression ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cell Type ◽  
Expression Levels

Multivariate analysis of expression of the microtubule-associated protein, tau, predicts improved progression free and overall survival in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 543-543
Author(s):  
A. M. Gown ◽  
L. C. Goldstein ◽  
P. L. Porter ◽  
R. B. Livingston ◽  
S. Tam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Progression Free Survival ◽  
High Expression ◽  
Breast Cancers ◽  
Beta Tubulin ◽  
Ki 67 ◽  
Expression Levels ◽  
Her 2

543 Background: Drugs that poison the mitotic spindle, including taxanes and vinca alkaloids, are active agents against breast cancer. Preliminary evidence showed that high expression levels of tau predicted improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. We now tested whether levels of tau and another microtubule associated protein, beta-tubulin, could predict PFS and OS in multivariate analysis using other prognostic marker studies, including ER, PR, p53 and Ki-67 on a tissue microarray (TMA) obtained from patients in the SWOG S0102 trial. Materials and Methods: Immunohistochemistry (IHC) using antibodies to tau, beta-tubulin, ER, PR, p53, and Ki-67 was performed on a TMA constructed from the S0102 paraffin blocks. All markers were scored semiquantitatively from 0 to 3. Progression free survival (PFS) and overall survival (OS) were evaluated using multivariate analysis. Results: A total of 38 patients (41.3%) were evaluated. Tau was positively correlated with ER (r=0.36; p=0.0325) and PR (r=0.63; p<0.0001), but not with beta tubulin (p=0.34), Ki-67 (p=0.58), or age (p=0.73). Beta tubulin was not significantly correlated with any other markers. Adjusting for age, there was a significant effect of tau expression on OS (HR=0.667, p= 0.0193) and PFS (HR=0.653; p=0.0035), with higher tau associated with longer survival. When adjusted for both age and PR, there was a marginally significant effect of tau on OS (HR=0.582; p=0.056) and PFS (HR=0.604; p= 0.065). Beta tubulin was not associated with OS (HR=0.909; p=0.66) and PFS (HR=0.904; p=0.58) adjusted for age. Conclusions: In multivariate analysis, identification of breast cancer specimens showing high expression levels of tau predicts improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. High expression of tau also correlated with PR and ER expression. These results confirm and expand earlier studies of the predictive power of tau in a multivariate analysis using a panel of IHC markers for breast cancer. No significant financial relationships to disclose.

scholarly journals Role of AmpR in the High Expression of the Plasmid-Encoded AmpC β-Lactamase CFE-1

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Ryuichi Nakano ◽  
Akiyo Nakano ◽  
Hisakazu Yano ◽  
Ryoichi Okamoto
Keyword(s):  
High Resistance ◽  
High Expression ◽  
Regulator Gene ◽  
High Level Expression ◽  
Expression Levels ◽  
High Level ◽  
Unique Plasmid

ABSTRACT CFE-1 is a unique plasmid-encoded AmpC β-lactamase with the regulator gene ampR. It imparts high resistance to most cephalosporins with constitutive high-level β-lactamase activity. CFE-1 is a unique plasmid-encoded AmpC β-lactamase with the regulator gene ampR. It imparts high resistance to most cephalosporins with constitutive high-level β-lactamase activity. Here, the β-lactamase activities and expression levels of ampC with or without ampR were investigated. Results suggested that the resistance of CFE-1 to cephalosporins is caused by a substitution in AmpR, in which the Asp at position 135 is modified to Ala to allow the constitutive high-level expression (derepression) of ampC.

scholarly journals Prognosis and functional role of EIF4G1 in lung squamous cell carcinoma

2021 ◽  
Author(s):  
Baoxin Bai ◽  
Lingwei Wang ◽  
Zhiyuan Huang ◽  
Zhiwen Zhang ◽  
Ying Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Functional Role ◽  
Lung Squamous Cell Carcinoma ◽  
High Expression ◽  
Expression Levels

Abstract Purpose To study the functional role and prognosis of EIF4G1 in lung squamous cell carcinoma (LSCC). Methods The clinical relevance of EIF4G1 in LSCC was investigated following detection of the expression levels of EIF4G1 by immunohistochemical staining (IHC). The expression levels of EIF4G1, AKT2, p-AKT, mTOR, cyclin D1 and β-actin were detected by western blot analysis. The cell proliferation and colony formation assays were used to detect the cell proliferative ability; flow-cytometry was used to assess the cell cycle; an invasion assay was used to detect cell invasive ability and the real-time quantitative polymerase chain reaction (Q-PCR) assay was used to assess the expression levels of EIF4G1 and β-actin. The role of EIF4G1 was verified by xenograft models. These experimental methods were employed to assess the functional role of EIF4G1 in LSCC pathogenesis. Results EIF4G1 was overexpressed in LSCC tumor tissues (P < 0.05) compared with the corresponding expression noted in paired adjacent tissues and cells. The expression levels of EIF4G1 were dependent on age (P = 0.002) and clinical stage (I vs II vs III + IV) (P < 0.001). High expression of EIF4G1 (P = 0.008, HR = 2.277, 95% CI = 1.250–4.145) could be used to predict the overall survival of LSCC patients as determined by the Cox’s proportional hazard model. High expression of EIF4G1 exhibited a lower survival (LogRank = 7.167, P = 0.007) in LSCC. Downregulation of EIF4G1 significantly inhibited LSCC proliferation, invasion and cell cycle progression. Conclusion EIF4G1 promotes LSCC cell proliferation and may represent an indicator of prognosis in LSCC.

Expression patterns of auxin-responsive genes during tomato flower pedicel abscission and potential effects of calcium

2012 ◽  
Vol 60 (1) ◽  
pp. 68 ◽  
Author(s):  
Xianhong Zuo ◽  
Tao Xu ◽  
Mingfang Qi ◽  
Shuangshuang Lv ◽  
Jinhong Li ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Negative Regulator ◽  
High Expression ◽  
Rna Expression ◽  
Conserved Domains ◽  
Expression Levels ◽  
Low Levels

This study aimed to determine the expression patterns of auxin (Aux/IAA)-responsive genes (ARG) during tomato flower pedicel abscission and the role of calcium in this auxin-mediated abscission. Most of the 19 proteins encoded by SlIAA genes showed the presence of all four conserved domains (I, II, III and IV). Expressions of some SlIAA genes decreased significantly (SlIAA 1, 3, 5, 8, 9, 10, 16, 17 and 27), while others increased (SlIAA 2, 4, 6, 7, 11, 12, 13, 26 and 29) at 0.5 h after excision. Most SlIAA genes were significantly upregulated at 1 h (except 9 and 27) then decreased to relatively low levels until 4 h after excision (except 4, 5, 8, 12, 14, 26 and 29). The SIAA genes were analysed and screened based on their expression patterns during different abscission phases. SlIAA4, 6, 9, 12 and 27 had relatively high expression levels consistent with the abscission rate, indicating potential roles in mediating abscission. SlIAA2, 3, 4, 5, 7, 9, 12, 13, 14, 16, 17, 26, 27 and 29 may have been important in delaying abscission, while SlIAA1, 9 and 12 may have been required for the completion of ethylene-induced abscission. SlIAA4, 6, 7, 8, 14, 16, 17 and 29 were important in calcium-delayed abscission. Analysis of other ARG revealed that tomato GH3 may have acted as an effective negative regulator in IAA-induced delay in abscission, while small auxin-up RNA expression patterns indicated that it may be a marker of IAA level throughout the abscission process.

scholarly journals IMMU-35. COMPLEMENT SYSTEM AND GLIOBLASTOMA: AN INTRICATE RELATIONSHIP

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi126-vi126
Author(s):  
Sandeep Mittal ◽  
Shayak Sengupta ◽  
Sabbir Khan ◽  
Kain McGee ◽  
Kristin Alfaro-Munoz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Complement System ◽  
Complement Activation ◽  
Receptor Expression ◽  
High Expression ◽  
Rt Pcr ◽  
Expression Levels ◽  
Human Gbm ◽  
The Complement System

Abstract The complement system is a vital part of the innate immune system which plays a critical role in immune surveillance and inflammatory processes. Malignant and host cells express various complement inhibitory proteins on their surface to protect against complement mediated cytotoxicity. Imbalanced complement activation triggers inflammation and alters the tumor microenvironment. Complement activation has been shown to induce proliferation and migration of breast, ovarian and lung cancer cells. At this time, the expression and functional role of the complement cascade in glioblastoma (GBM) remain elusive. Here, we investigated the role of complement proteins and their receptor expression in human primary glioma stem-like cells (GSCs) and human GBM tissues. Western blot data demonstrated a high level of expression of central complement components and their receptors in GSCs. RT-PCR data further confirmed the high expression of complement genes which was similar or higher to normal human astrocytes (HA), a cell with high baseline expression levels of complement genes. Flow cytometry analysis revealed that almost 95% of GSCs expressed the anaphylatoxin complement receptors C3aR and C5aR on their cell surfaces which was consistent with our immunohistochemistry analysis of freshly resected GBM tissues. Furthermore, anaphylatoxin C5a exposure increased the proliferation of a subgroup of GSCs while reduced in another subset. Interestingly, C5a exposure was found to increase the expression of various pro-inflammatory markers in GSCs with reduced proliferation. Fluorescence-activated cell sorting (FACS) analysis of freshly isolated human GBM tissue revealed predominant expression of C5aR on cancer cells (CD11b-/CD45- cells) rather than on immune cells. RT-PCR analysis also demonstrated high expression levels of complement genes with concomitant decrease in complement inhibitory genes in human GBM tissue. Evaluation of the differential role of the complement system in GSCs along with their role in in vivo glioma models is ongoing.

HER3 as a potential prognostic biomarker in pancreatic cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 295-295 ◽  
Author(s):  
Andrea Wang-Gillam ◽  
Victoria Rimkunas ◽  
Adnan Abu-Yousif ◽  
Timothy M. Nywening ◽  
Feng Gao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Membrane ◽  
Clinical Information ◽  
Human Pancreatic Cancer ◽  
Rank Test ◽  
Membrane Expression ◽  
Expression Levels ◽  
Her Family ◽  
Survival Difference

295 Background: HER 3 is revealing itself to be increasingly important in HER family signaling. Understanding the role of HER 3 in pancreatic cancer may shed light on targeted therapy development. Methods: A large human pancreatic cancer tumor tissue microarray (TMA) was established at our institution from 165 patients with pancreatic cancer who underwent surgical resection. The TMA contains two cores from each patient. Clinical information of these patients has been prospectively maintained in a clinical database. Immunohistochemistry (IHC) was performed on the TMA using a monoclonal antibody against HER 3. An independent pathologist blinded to the patient data applied the H score to grade the expression level of HER 3. The association between expression levels of HER 3 and survival were evaluated by the Kaplan-Meyer product limit method and log-rank test, while the optimal cut-off for each marker was determined using the Martingale residuals from Cox proportional hazard models. Results: Out of 165 patients, 136 patients’ tumors were identified to have adequate tumor content for IHC analysis. The group with higher HER 3 levels at the cell membrane (n=50)(H score ≥150) had a superior overall survival compared to the low HER 3 membrane expression group (n=86) (22.5 months vs. 17 months; p=0.036). Interestingly, the group with higher expression levels at both the cell membrane and in the cytosol (n=37) (H score ≥190) had a more striking survival difference compared to the lower group (n=99) (26 months vs. 15 months; p= 0.035). Conclusions: Patients with high HER 3 expression either at the cell membrane only or at both the membrane and in the cytosol have longer survival, perhaps indicating a lower heregulin and inactive HER 3 signaling. Additional biomarker analyses are ongoing. The functional role of HER 3 in pancreatic cancer is being further explored to assist clinical evaluation of HER 3 targeting in pancreatic cancer.

Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis

2004 ◽  
Vol 18 (11) ◽  
pp. 1240-1242 ◽  
Author(s):  
Merav Darash-Yahana ◽  
Eli Pikarsky ◽  
Rinat Abramovitch ◽  
Evelyne Zeira ◽  
Boaz Pal ◽  
...  
Keyword(s):  
Tumor Growth ◽  
High Expression ◽  
Expression Levels

scholarly journals Diagnostic and Prognostic Role of Preoperative Circulating CA 15-3, CA 125, and Beta-2 Microglobulin in Renal Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Giuseppe Lucarelli ◽  
Pasquale Ditonno ◽  
Carlo Bettocchi ◽  
Antonio Vavallo ◽  
Monica Rutigliano ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Serum Proteins ◽  
Ca 125 ◽  
Cancer Specific Survival ◽  
Fuhrman Grade ◽  
Visceral Metastases

CA 15-3, CA 125 andβ-2 microglobulin are three common tumor markers currently used for diagnosis, prognosis, assessment of therapeutic response, and/or to evaluate recurrence in breast and ovarian cancer and malignant lymphoproliferative disorders, respectively. In the present prospective study we assessed the role of these three serum proteins as biomarkers for renal cell carcinoma (RCC), as well as any association between tumor marker levels and clinical-pathological parameters. CA 15-3, CA 125, andβ-2 microglobulin were preoperatively measured in 332 patients who underwent nephrectomy for RCC. Estimates of cancer-specific survival (CSS) was calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS. Preoperatively, 35.2% (n=117), 9.6% (n=32) and 30.4% (n=101) of the patients had abnormal levels of CA 15-3, CA 125 andβ-2 microglobulin, respectively. Statistically significant differences resulted between CA 15-3, CA 125 andβ-2 microglobulin values and tumor size, Fuhrman grade, presence of lymph node, and visceral metastases. CSS was significantly decreased for patients with high levels of CA 15-3, CA 125, andβ-2 microglobulin (P<0.0001,P<0.0001,andP=0.001, resp.). At multivariate analysis only age, the presence of visceral metastases, and high levels of CA 15-3 were independent adverse prognostic factors for CSS.

The Role of Family Members in Safer/Unsafe Injection Drug Use Practices

2011 ◽  
Author(s):  
L. Jackson ◽  
M. Dykeman ◽  
J. Gahagan ◽  
J. Karabanow ◽  
J. Parker
Keyword(s):  
Drug Use ◽  
Injection Drug Use ◽  
Family Members ◽  
Injection Drug ◽  
Unsafe Injection
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